VCV000159301.28 - ClinVar

NM_022455.5(NSD1):c.3106G>C (p.Ala1036Pro)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022455.5(NSD1):c.3106G>C (p.Ala1036Pro)

Variation ID: 159301 Accession: VCV000159301.28

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q35.3 5: 177211505 (GRCh38) [ NCBI UCSC ] 5: 176638506 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 23, 2014	May 1, 2024	Nov 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_022455.5:c.3106G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071900.2:p.Ala1036Pro	missense
NM_001365684.2:c.2233G>C	NP_001352613.2:p.Ala745Pro	missense
NM_001409301.1:c.3106G>C	NP_001396230.1:p.Ala1036Pro	missense
NM_001409302.1:c.3106G>C	NP_001396231.1:p.Ala1036Pro	missense
NM_001409303.1:c.3106G>C	NP_001396232.1:p.Ala1036Pro	missense
NM_001409304.1:c.2686G>C	NP_001396233.1:p.Ala896Pro	missense
NM_001409305.1:c.2353G>C	NP_001396234.1:p.Ala785Pro	missense
NM_001409306.1:c.2233G>C	NP_001396235.1:p.Ala745Pro	missense
NM_001409307.1:c.2233G>C	NP_001396236.1:p.Ala745Pro	missense
NM_001409308.1:c.2233G>C	NP_001396237.1:p.Ala745Pro	missense
NM_001409309.1:c.2233G>C	NP_001396238.1:p.Ala745Pro	missense
NM_172349.5:c.2233G>C	NP_758859.2:p.Ala745Pro	missense
NC_000005.10:g.177211505G>C
NC_000005.9:g.176638506G>C
NG_009821.1:g.83427G>C
LRG_512:g.83427G>C
LRG_512t1:c.3106G>C	LRG_512p1:p.Ala1036Pro
	Q96L73:p.Ala1036Pro

... more HGVS ... less HGVS

Protein change

A767P, A745P, A785P, A896P

Other names

Canonical SPDI

NC_000005.10:177211504:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.02364

Trans-Omics for Precision Medicine (TOPMed) 0.02390

1000 Genomes Project 30x 0.02561

The Genome Aggregation Database (gnomAD) 0.02602

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.02630

The Genome Aggregation Database (gnomAD), exomes 0.02273

Links

ClinGen: CA248755 UniProtKB: Q96L73#VAR_015778 dbSNP: rs28932179 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
NSD1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1757	1874

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (7)	criteria provided, multiple submitters, no conflicts	Mar 25, 2015	RCV000146803.27
Inborn genetic diseases	Benign (1)	criteria provided, single submitter	Jun 29, 2016	RCV002312651.9
not provided	Benign (2)	criteria provided, single submitter	Mar 3, 2015	RCV001573348.11
Sotos syndrome	Benign (3)	criteria provided, multiple submitters, no conflicts	Nov 14, 2023	RCV003231203.10

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Feb 08, 2013)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	not specified (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000194129.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014
Benign (Mar 25, 2015)	criteria provided, single submitter (DGD Variant Analysis Guidelines) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV000258190.2 First in ClinVar: Jun 29, 2015 Last updated: Jun 29, 2015
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000314058.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Apr 07, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000203155.7 First in ClinVar: Jan 29, 2015 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NSD1 Number of individuals with the variant: 6 Sex: mixed
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001890562.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: This variant is associated with the following publications: (PMID: 27153395, 27058611)
Benign (Nov 03, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	None Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000558229.6 First in ClinVar: Apr 17, 2017 Last updated: Feb 07, 2023
Benign (Jun 29, 2016)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000846953.5 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Jul 15, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Sotos syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002054861.1 First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022
Benign (Nov 14, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	Sotos syndrome Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV004563914.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001799102.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001971344.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001930763.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952882.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NSD1	-	-	-	-

Text-mined citations for rs28932179 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_022455.5(NSD1):c.3106G>C (p.Ala1036Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs28932179 ...